==== Reference: Usmani SS, Bedi G, Samuel JS, Singh S, Kalra S, Kumar P, et al. (2017) THPdb: Database of FDA-approved peptide and protein therapeutics. PLoS ONE 12(7) e0181748.====

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1708 details
Primary information
ThPP IDTh1170
Therapeutic Peptide/Protein NameBlinatumomab
SequenceDIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPPKL view full sequnce in fasta
Functional ClassificationIIIc
Molecular Weight54100.0
Chemical FormulaC2367H3577N649O772S19
Isoelectric PointNA
HydrophobicityNA
Melting Point (℃)NA
Half Life2.11 hours, standard deviation 1.42.
DescriptionBlinatumomab is a BiTE-class (bi-specific T-cell engagers) constructed monoclonal antibody indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). Blinatumomab is manufactured by Amgen Inc. and marketed under the brand Blincyto™. A full treatment regimen consisting of two cycles of four weeks each, is priced at $178 000 USD. Blinatumomab was approved in December 2014 under the FDA’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients.
Indication/DiseaseIndicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
Pharmacodynamics NA
Mechanism of ActionBlinatumomab is a bispecific CD19-directed CD3 T-cell engager that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells. It activates endogenous T cells by connecting CD3 in the T-cell receptor (TCR) complex with CD19 on benign and malignant B cells. Blinatumomab mediates the formation of a synapse between the T cell and the tumor cell, upregulation of cell adhesion molecules, production of cytolytic proteins, release of inflammatory cytokines, and proliferation of T cells, which result in redirected lysis of CD19+ cells.
Toxicity Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving blinatumomab. Interrupt or discontinue blinatumomab as recommended. - Neurological toxicities, which may be severe, life-threatening, or fatal, occurred in patients receiving blinatumomab. Interrupt or discontinue blinatumomab as recommended. - In patients receiving blinatumomab in clinical trials, serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections were observed in approximately 25% of patients, some of which were life-threatening or fatal. - Tumor lysis syndrome (TLS), which may be life-threatening or fatal, has been observed in patients. - Neutropenia and febrile neutropenia, including life-threatening cases, have been observed in patients. - Treatment with blinatumomab was associated with transient elevations in liver enzymes. - Cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving blinatumomab, especially in patients with prior treatment with cranial irradiation and antileukemic chemotherapy (including systemic high-dose methotrexate or intrathecal cytarabine).
MetabolismThe metabolic pathway of blinatumomab has not been characterized. Like other protein therapeutics, blinatumomab is expected to be degraded into small peptides and amino acids via catabolic pathways.
AbsorptionNA
Volume of Distribution4.52 L, standard deviation 2.89.
Clearance2.92 L/hour, standard deviation 2.83.
CategoriesAntineoplastic Agents, Immunosuppressive Agents, Monoclonal antibodies, Antineoplastic and Immunomodulating Agents
Patents NumberUS20120328618
Date of Issue27/10/09
Date of Expiry27/10/29
Drug InteractionThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Clozapine; The risk or severity of adverse effects can be increased when Denosumab is combined with Blinatumomab; The risk or severity of adverse effects can be increased when Blinatumomab is combined with Leflunomide; The risk or severity of adverse effects can be increased when Metamizole is combined with Blinatumomab; The risk or severity of adverse effects can be increased when Blinatumomab is combined with Natalizumab; The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Blinatumomab; Roflumilast may increase the immunosuppressive activities of Blinatumomab; The therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Blinatumomab; The risk or severity of adverse effects can be increased when Tacrolimus is combined with Blinatumomab; Blinatumomab may increase the immunosuppressive activities of Tofacitinib.
Target B-lymphocyte antigen CD19; T-cell surface glycoprotein CD3 delta chain
Information of corresponding available drug in the market
Brand NameBlincyto
CompanyAMGEN
Brand DiscriptionBLINCYTO (blinatumomab) is a bispecific CD19-directed CD3 T-cell engager that binds to CD19 (expressed on cells of B-lineage origin) and CD3 (expressed on T cells). BLINCYTO is produced in Chinese hamster ovary cells. It consists of 504 amino acids
Prescribed forBLINCYTO is indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
Chemical NameNA
Formulation12.5 mcg/mL
Physcial Appearncelyophilized powder for intravenous administration
Route of AdministrationIntravenous
Recommended DosageA single cycle of treatment of BLINCYTO consists of 4 weeks of continuous intravenous infusion followed by a 2-week treatment-free interval. For patients at least 45 kg in weight: In Cycle 1, administer BLINCYTO at 9 mcg/day on Days 1–7 and at 28 mcg/day on Days 8–28. For subsequent cycles, administer BLINCYTO at 28 mcg/day on Days 1–28. Allow for at least 2 weeks treatment-free between cycles of BLINCYTO. A treatment course consists of up to 2 cycles of BLINCYTO for induction followed by 3 additional cycles for consolidation treatment (up to a total of 5 cycles).
ContraindicationBLINCYTO is contraindicated in patients with known hypersensitivity to blinatumomab or to any component of the product formulation.
Side EffectsCytokine Release Syndrome; Neurological Toxicities; Infections; Tumor Lysis Syndrome; Neutropenia and Febrile Neutropenia; Effects on Ability to Drive and Use Machines; Elevated Liver Enzymes; Leukoencephalopathy; Preparation and Administration Errors.
Useful Linkhttp://www.rxlist.com/blincyto-drug.htm
PubMed ID28273376, 28096698, 27521873, 27011303, 26667979, 26525683, 26448656, 25999456, 25900401
3-D StructureTh1170 (View) or (Download)